FIELD OF THE INVENTION
This invention relates to an absorbable/biodegradable, radially fluted, tubular stent having grooves or flutes along its entire length for expansion to a predetermined range of diameters, depending on the number and variability in the shape and depth of the flutes or grooves, after deployment, using a balloon-catheter, in a tubular body lumen through outward deformation of said grooves to yield an essentially circular cross-section to stabilize the internal dimensions of the treated conduit or lumen as in the case of an endovascular stent that is used in preventing vascular restenosis.
BACKGROUND OF THE INVENTION
Stents, including cardiovascular and biliary stents, are well known as devices that are used to support a body lumen, such as an artery, vein, biliary duct, or esophagus. They may be employed as a primary treatment for a construction of a body lumen (stenosis), or may be used following a medical procedure, such as angioplasty, used to remedy stenosis.
Conventional stents have taken two forms. First, there are the self-expanding stents that typically are made of metal and that may include a biocompatible coating. Such stents are permanently implanted into the human body by deploying them on or through a catheter, although removable stents of this kind are known to the art. The stent, which may be woven, strutted, or wound like a spring, is placed in tension or compression along the inner or outer perimeter of the catheter, and percutaneously inserted into the body where it is guided to the site of implantation. The stent then is released from the perimeter of the catheter, or extruded from the interior of the catheter, where it expands to a fixed, predetermined diameter, and is held in position as a result of that expansion. Many different configurations of such self-expanding stents, and of catheters used to deploy such stents, are known to the art.
One variation on these self-expanding stents is illustrated in Kawai et al., U.S. Pat. No. 4,950,258. Kawai discloses the use of a spring-like coil of plastic having “shape memory.” The stent is manufactured to a desired size from homopolymers or copolymers of lactide and/or glycolide, and then compressed under suitable conditions for insertion into the body. Thereafter, the stent is heated, and because of “shape memory,” returns to its original (uncompressed) size.
A second type of stent commonly used in the field is expandable as a result of mechanical action by the surgeon. One such stent is disclosed in Palmaz, U.S. Pat. Nos. 4,733,665, 4,776,337, and 4,639,632. According to the Palmaz patents, an unexpanded stent is permanently implanted in the body by percutaneously inserting it into a vessel using a catheter, and guiding the stent to the site where it is to be permanently implanted. Upon reaching the site of implantation, the balloon portion of the catheter is expanded and concomitantly a portion of the stent also is expanded solely as a result of the mechanical force applied by the expanding balloon, until the stent is sized appropriately for the implantation site. Thereafter, the expanded balloon is deflated, and the catheter is removed from the body, leaving the stent held permanently in position. The stents disclosed in Palmaz are made of a metal or a nondegradable plastic and, to achieve compatibility with and in the body, the stent may be coated with a biologically compatible substance.
Commercially available stents of the types described above exhibit undesirable characteristics that the art has sought to overcome. Self-expanding stents may be inappropriately sized for the sites where they are to be deployed, increasing the risk of rupture, stent migration, stenosis, and thrombosis as the stent continually tries to expand after deployment to its predetermined, optimal diameter. Conversely, a stent sized too small for the lumen may project into the lumen, thereby causing a primary or secondary obstruction or migration. Both self-expanding and expandable stents that are know in the art, because they are designed for permanent implantation in the body, increase the risk of restenosis, thrombosis, or other adverse medical effects because of the risk of adverse reaction by surrounding tissue, adverse reaction by the material flowing through the body lumen (such as blood or blood products), and deterioration of surrounding tissue and/or the stent itself. The metals or alloys used for such stents, because they are believed to be biologically stable, also remain in the body for the patient's life, unless surgically removed at a later date along with surrounding tissue. Thus, these stents do not permit temporary placement within the body unless patient and surgeon are prepared to undertake a second procedure to remove the stent, which is difficult or impossible in most cases.
Conventional balloon-deployed stents, like that described by Palmaz, also require an extensively perforated structure that can be mechanically expanded intraluminally by a balloon catheter without applying forces that are potentially threatening to the surrounding tissue. Such perforations also permit cell growth to occur from the intima or media lining the lumen. Thus, for example, endothelial cells and smooth muscle fibroblasts migrate through the perforations inside and around stents like that shown in Palmaz. Such endothelial cell growth is desirable to the extent that the endothelial layer inhibits the formation of blood clots (thrombogenesis) by providing a blood-compatible surface. However, vascular smooth muscle cell migration and proliferation may be undesirable when it is uncontrolled (as in intimal hyperplasia) and results in the occlusion of the lumen that has been surgically opened by placement of the stent. Thus, stents such as that described by Palmaz may be undesirable when the risk of intimal hyperplasia is substantial. The benefits of a balloon-deployed stent, therefore, may not be realized in such circumstances. Moreover, to the extent that the design of stents such as those described in Palmaz are dictated primarily by mechanical considerations, such as the forces needed to open the stent, biological considerations (such as designing the stent to limit cell ingrowth and migration, for example) frequently play a secondary role or no role at all.
Still another disadvantage of existing stents is that the materials from which they are made are rigid, and therefore, the compliance of the stents (i.e., the ability to control the flexibility of the material used to design stents for particular applications) is limited. This has the disadvantage of exposing patients to risks associated with the placement of a device that may exhibit a rigidity in excess of that needed for the particular application.
Most conventional stents also are capable of being used as drug delivery systems when they are coated with a biodegradable coating that contains the drug to be delivered. The amount of the drug that can be delivered, and the time over which it may be released, therefore, may be limited by the quality of coating employed.
Beck et al., U.S. Pat. No. 5,147,385, discloses the use of a degradable, mechanically expandable stent prepared from poly(ε-caprolactone) or similar polymers that melt between 45°-75° C., because the melted polymer may be expanded in such a manner as to adapt to the body lumen in which it is deployed. At the same time, because poly(ε-caprolactone) enters a liquid phase in the temperature range that Beck discloses (at about 60° C.), the ability to achieve controlled, improved strength characteristics using the stent described by Beck is limited. Furthermore, the temperature range described by Beck et al. is well above the glass-transition temperature of poly(ε-caprolactone). This limits the ability of a stent made according to Beck et al. to resist radially compressive forces imparted by the lumen upon the stent without creeping or relaxing, introducing a substantial risk of occluding the lumen. Alternatively, one might use massive structures made according to Beck et al. to keep the lumen open, but in so doing, the normal function of the lumen would be perturbed significantly, possibly creating regions where flow of body liquids through the lumen would be severely restricted or stagnate, so that clots may form in those regions.
Slepian et al., U.S. Pat. No. 5,213,580, discloses an endoluminal sealing process using a poly(caprolactone) material that is flowable at temperatures above 60°-80° C. According to Slepian, this flowable material is able to conform to irregularities on the inner surface of the body lumen in which it is deployed.
Goldberg et al., U.S. Pat. No. 5,085,629, discloses the manufacture of a urethral stent made from a terpolymer of l-lactide, glycolide, and ε-caprolactone, which is selected to permit the stent to degrade within the body. Goldberg does not, however, disclose the use of an expandable stent, nor does Goldberg et al. provide any information regarding the design of the stent or its method of deployment within the body.
U.S. Pat. No. 6,248,129 B discloses an expandable, biodegradable stent for use within a body lumen comprising a hollow tube made from a copolymer of l-lactide and ε-caprolactone that, in expanded form, is of a first diameter sufficient to be retained upon a balloon catheter for placement within the body lumen, and that is not plastically expandable at normal body temperatures, and that is expandable using thermo-mechanical means at a temperature between about 38°-55° C. when the balloon catheter is inflated to a second diameter sufficient to be retained within the body lumen. However, it is believed by the present inventor that (1) the temperature required for expansion is close to 55° C. and can damage the vital tissue; and (2) the mechanical stability of the expanded configuration would be far less than optimal as one recognizes the stress-relaxation of a device having such shape.
U.S. Pat. No. 5,670,161 discloses a stent comprising a hollow, substantially cylindrical member formed of a biocompatible composition, said composition being in the form of a polymer matrix and at least one medical agent in a weight up to 90 percent of the total weight of the member dispersed uniformly through the polymer matrix, whereby when the stent is disposed in the lumen of the blood vessel, at least one medical agent is released at a controlled release rate from the member into the vessel, it must be dissolved in the polymer matrix and thereafter diffuse through the polymer matrix, and the controlled release rate extending over a period of time after the lumen stent is inserted into the vessel and being controlled solely by the rate of diffusion of the medical agent from the stent. However, it is believed by the present inventor that the force required to expand the stent subject of U.S. Pat. No. 5,670,161 would exceed that usually encountered during angioplasty.
Thus, a stent that overcomes the problems just identified, while at the same time providing or enhancing the benefits that result from the use of stents, is needed to improve patient safety and recovery. This provided the incentive to pursue the subject of the present invention.
SUMMARY OF THE INVENTION
The present invention is directed an absorbable, biodegradable, radially fluted, tubular polymeric stent having at least two grooves extending along its entire length for expansion after deployment through outward deformation of the grooves to yield an essentially circular cross-section. In a preferred embodiment the stent has from 3 to 12 grooves extending along the entire length thereof.
Preferably, the stent is formed of an absorbable crystalline polyester having chain sequences derived from at least one cyclic monomer such as l-lactide, glycolide, p-dioxanone, trimethylene carbonate, ε-caprolactone, morpholine-2,5-dione. In one embodiment one of the segments/blocks is amorphous and another of the segments/blocks is crystalline. In one embodiment the copolyester has a monocentric polyaxial amorphous core having the crystalline segments/blocks extending outward therefrom.
In a preferred embodiment the stent is formed of a segmented/block copolyester wherein one of the segments/blocks is crystalline and exhibits a melting temperature (Tm) of less than about 110° C. and another crystalline segment/block exhibits a melting temperature (Tm) of from about 140° C. to about 220° C. For such embodiment that copolyester may be based on a monocentric polyaxial system having polyaxial core segments with segments/blocks extending outwardly therefrom, wherein the core segments have a lower melting temperature (Tm) than the outwardly extending segments/blocks.
In another embodiment the inventive stent is formed of a blend of at least two absorbable polymers which are a dispersed phase of crystalline microrods in an amorphous matrix.
In yet another embodiment the present inventive stent is formed of a blend of at least two absorbable polymers comprising a dispersed phase of crystalline microrods in a matrix, wherein the microrods exhibit a higher degree of crystallinity than the matrix.
In a still further embodiment the present inventive stent is formed of a chitosan-based material, preferably an acylated chitosan, coated with an absorbable polyester.
In one embodiment the outer wall of the unexpanded stent has radially extending barbs to restrict movement of the deployed expanded stent.
Preferably, the present stent is made by a which includes the steps of forming an unfluted tube and thermoforming the grooves therein. The step of forming an unfluted tube may be achieved by a variety of means such melt-extrusion or electrostatic spinning of a viscous solution of the constituent polymer or polymer blend. The latter process step produces a microporous structure. For such embodiment the viscous solution may be formed of chitosan-based materials, and the process may further include the step of coating the formed tube with an absorbable polyester coating. Preferably the tube is acylated prior to coating.
In another preferred embodiment the present inventive stent is made by injection molding.
The present inventive stent is especially suitable for use in vascular and urinogenital applications.
For many applications it is preferred that the stent contains at least one bioactive agent for preventing restenosis and infection. For some applications it is preferred that the stent contains at least 10 percent by weight of an inorganic radiopacifier.
The present invention also is directed to an absorbable, expandable, unfluted, tubular polymeric stent having radially extending barbs. Preferably the wall of the unexpanded form of this stent is perforated. As with the embodiments discussed above, it is preferred that this stent is formed of a segmented/block copolymer.